Development of new rationales for the hormonal therapy of prostatic cancer may lead to improvements in the prognosis for this disease. This process will require an in depth understanding of the physiological and pharmacological effects of estrogen on the tissues of the male reproductive tract. The physiological role of endogenous estrogen in maintenance of normal tissue function and the pharmacological role of administered estrogen in induction of stromal hyperplasia and epithelial metaplasia will be analyzed by pharmacological and biochemical methods using the guinea pig seminal vesicle as a model system. This tissue provides a unique opportunity to easily analyze epithelial and stromal components of the gland as separate functional entities. Specific anti-estrogens (Tamoxifen), and aromatase inhibitors, inhibitors of estrogen synthesis (4-hydroxy-androstene-3,17-dione), will be used to antagonize the effects of endogenous and administered estrogens. Endpoints of estrogenic action to be evaluated are: androgen and progesterone receptor levels; general and specific protein synthesis; and collagen, membrane lipid and DNA synthesis. The physical, kinetic and binding properties of multiple estrogen binding activities will also be examined in order to substantiate their role as receptors mediating the actions of estrogen in this tissue. The proposed research will provide new insights into the multi-hormonal regulation of sex accessory tissue function, and thus, will foster continued progress towards understanding the role of estrogen in the etiology and treatment of benign and malignant prostatic disease.